Bidirectional Neural Interface Research Articles

Transforming the Anthropomorphic Passive Free-Flow Foot Prosthesis Into a Powered Foot Prosthesis With Intuitive Control and Sensation (Bionic FFF).

Approximately 89% of all service members with amputations do not return to duty. Restoring intuitive neural control with somatosensory sensation is a key to improving the safety and efficacy of prosthetic locomotion. However, natural somatosensory feedback from lower-limb prostheses has not yet been incorporated into any commercial prostheses. We developed a neuroprosthesis with intuitive bidirectional control and somatosensation and evoking phase-dependent locomotor reflexes, we aspire to significantly improve the prosthetic rehabilitation and long-term functional outcomes of U.S. amputees. We implanted the skin and bone integrated pylon with peripheral neural interface pylon into the cat distal tibia, electromyographic electrodes into the residual gastrocnemius muscle, and nerve cuff electrodes on the distal tibial and sciatic nerves. Results. The bidirectional neural interface that was developed was integrated into the existing passive Free-Flow Foot and Ankle prosthesis, WillowWood, Mount Sterling, OH. The Free-Flow Foot was chosen because it had the highest Index of Anthropomorphicity among lower-limb prostheses and was the first anthropomorphic prosthesis brought to market. Conclusion. The cats walked on a treadmill with no cutaneous feedback from the foot in the control condition and with their residual distal tibial nerve stimulated during the stance phase of walking.

Hydrogel-Integrated Multimodal Response as a Wearable and Implantable Bidirectional Interface for Biosensor and Therapeutic Electrostimulation.

A hydrogel that fuses long-term biologic integration, multimodal responsiveness, and therapeutic functions has received increasing interest as a wearable and implantable sensor but still faces great challenges as an all-in-one sensor by itself. Multiple bonding with stimuli response in a biocompatible hydrogel lights up the field of soft hydrogel interfaces suitable for both wearable and implantable applications. Given that, we proposed a strategy of combining chemical cross-linking and stimuli-responsive physical interactions to construct a biocompatible multifunctional hydrogel. In this hydrogel system, ureidopyrimidinone/tyramine (Upy/Tyr) difunctionalization of gelatin provides abundant dynamic physical interactions and stable covalent cross-linking; meanwhile, Tyr-doped poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) acts as a conductive filler to establish electrical percolation networks through enzymatic chemical cross-linking. Thus, the hydrogel is characterized with improved conductivity, conformal biointegration features (i.e., high stretchability, rapid self-healing, and excellent tissue adhesion), and multistimuli-responsive conductivity (i.e., temperature and urea). On the basis of these excellent performances, the prepared multifunctional hydrogel enables multimodal wearable sensing integration that can simultaneously track both physicochemical and electrophysiological attributes (i.e., motion, temperature, and urea), providing a more comprehensive monitoring of human health than current wearable monitors. In addition, the electroactive hydrogel here can serve as a bidirectional neural interface for both neural recording and therapeutic electrostimulation, bringing more opportunities for nonsurgical diagnosis and treatment of diseases.

Long Term Performance of a Bi-Directional Neural Interface for Deep Brain Stimulation and Recording.

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.Methods: Seven ovine subjects were implanted with deep brain stimulation (DBS) leads at different nodes within the Circuit of Papez: four with unilateral leads in the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® (Medtronic) or Percept PC°ledR (Medtronic) deep brain stimulation and recording device. Spontaneous local field potentials (LFPs), evoked potentials (EPs), LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up.

A Hybrid 1st/2nd-Order VCO-Based CTDSM With Rail-to-Rail Artifact Tolerance for Bidirectional Neural Interface

Bi-directional brain machine interfaces enable simultaneous brain activity monitoring and neural modulation. However stimulation artifact can saturate instrumentation front-end, while concurrent on-site recording is needed. This brief presents a voltage controlled-oscillator (VCO) based continuous-time <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\rm \Delta \Sigma $ </tex-math></inline-formula> modulator (CTDSM) with rail-to-rail input range and fast artifact tracking. A hybrid <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$1^{st}/2^{nd}$ </tex-math></inline-formula> -order loop is designed to achieve high dynamic range (DR) and large input range. Stimulation artifact is detected by a phase counter and compensated by the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$1^{st}$ </tex-math></inline-formula> -order loop. The residue signal is digitized by the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2^{nd}$ </tex-math></inline-formula> -order loop for high precision. Redundancy between the two loops is implemented as feedback capacitors elements with non-binary ratio to guarantee feedback stability and linearity. Fabricated in a 55-nm CMOS process, the prototype achieves 65.7dB SNDR across 10 kHz bandwidth with a full scale of 200 mV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">pp</sub> . And a ±1.2 V input range is achieved to suppress artifacts. Saline based experiment with simultaneous stimulation and recording demonstrates that the implemented system can track and tolerate rail-to-rail stimulation artifact within 30 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{s}$ </tex-math></inline-formula> while small neural signal can be continuously monitored.

A 3.1-5.2GHz, Energy-Efficient Single Antenna, Cancellation-Free, Bitwise Time-Division Duplex Transceiver for High Channel Count Optogenetic Neural Interface.

We report an energy-efficient, cancellation-free, bit-wise time-division duplex (B-TDD) transceiver (TRX) for real-time closed-loop control of high channel count neural interfaces. The proposed B-TDD architecture consists of a duty-cycled ultra-wide band (UWB) transmitter (3.1-5 GHz) and a switching U-NII band (5.2 GHz) receiver. An energy-efficient duplex is realized in a single antenna without power-hungry self-interference cancellation circuits which are prevalently used in the conventional full-duplex, single antenna transceivers. To suppress the interference between up- and down-links and enhance the isolation between the two, we devised a fast-switching scheme in a low noise amplifier and used 5× oversampling with a built-in winner-take-all voting in the receiver. The B-TDD transceiver was fabricated in 65 nm CMOS RF process, achieving low energy consumption of 0.32 nJ/b at 10 Mbps in the receiver and 9.7 pJ/b at 200 Mbps in the transmitter, respectively. For validation, the B-TDD TRX has been integrated with a μLED optoelectrode and a custom analog frontend integrated circuit in a prototype wireless bidirectional neural interface system. Successful in-vivo operation for simultaneously recording broadband neural signals and optical stimulation was demonstrated in a transgenic rodent.

A Bidirectional Neural Interface SoC With Adaptive IIR Stimulation Artifact Cancelers.

We present a 180-nm CMOS bidirectional neural interface system-on-chip that enables simultaneous recording and stimulation with on-chip stimulus artifact cancelers. The front-end cancellation scheme incorporates a least-mean-square engine that adapts the coefficients of a 2-tap infinite-impulse-response filter to replicate the stimulation artifact waveform and subtract it at the front-end. Measurements demonstrate the efficacy of the canceler in mitigating artifacts up to 700 mVpp and reducing the front-end amplifier saturation recovery time in response to a 2.5 Vpp artifact. Each recording channel houses a pair of adaptive infinite-impulse-response filters, which enable cancellation of the artifacts generated by the simultaneous operation of the 2 on-chip stimulators. The analog front-end consumes 2.5 μW of power per channel, has a maximum gain of 50 dB and a bandwidth of 9.0 kHz with 6.2 μVrms integrated input-referred noise.

A Single-Chip Bidirectional Neural Interface With High-Voltage Stimulation and Adaptive Artifact Cancellation in Standard CMOS

A single-chip, bidirectional brain–computer interface (BBCI) enables neuromodulation through simultaneous neural recording and stimulation. This article presents a prototype BBCI application-specified integrated circuit (ASIC) consisting of a 64-channel time-multiplexed recording front-end, an area-optimized four-channel high-voltage compliant stimulator, and electronics to support the concurrent multi-channel stimulus artifact cancellation. Stimulator power generation is integrated on a chip, providing ±11-V compliance from low-voltage supplies with a resonant charge pump. High-frequency (~3 GHz) self-resonant clocking is used to reduce the pumping capacitor area while suppressing the associated switching losses. A 32-tap least mean square (LMS)-based digital adaptive filter achieves 60-dB artifact suppression, enabling simultaneous neural stimulation and recording. The entire chip occupies 4 mm2 in a 65-nm low power (LP) process and is powered by 2.5-/1.2-V supplies, dissipating $205~\mu \text{W}$ in recording and $142~\mu \text{W}$ in the stimulation and cancellation back-ends. The stimulation output drivers achieve 31% dc–dc efficiency at a maximum output power of 24 mW.

A High DR, DC-Coupled, Time-Based Neural-Recording IC With Degeneration R-DAC for Bidirectional Neural Interface

The bidirectional neural interface is essential to realize the closed-loop neuromodulation, which is the core of next-generation neurological devices. For the bidirectional neural interface, a recording circuit with a high dynamic range (DR) is required to record the neural signal while stimulating the neuronal cells simultaneously. This article presents a voltage-controlled oscillator (VCO)-based neural-recording IC, which directly quantizes the input signal and achieves a large DR to process the small-amplitude neural signal in the presence of the large-amplitude stimulation artifact (SA). A feedback-controlled source degeneration is applied to the input transconductor circuit ( $G_{\mathrm {m, in}}$ ) by using a resistor digital-to-analog converter (R-DAC). It mitigates the circuit nonlinearity, resulting in a large signal-to-noise-and-distortion ratio (SNDR) and a high input impedance ( $Z_{\mathrm {in}}$ ). The implemented neural-recording IC achieves 81.3-dB SNDR over 200-Hz signal bandwidth and 200-mVpp maximum allowable input range with consuming 3.9 $\mu \text{W}$ per channel. The in-vitro measurement with prerecorded neural signal demonstrates that the original neural signal is well preserved in the presence of the large-amplitude artifact without any saturation or significant distortion.

A Chronically Implantable Bidirectional Neural Interface for Non-human Primates.

Optogenetics has potential applications in the study of epilepsy and neuroprostheses, and for studies on neural circuit dynamics. However, to achieve translation to clinical usage, optogenetic interfaces that are capable of chronic stimulation and monitoring with minimal brain trauma are required. We aimed to develop a chronically implantable device for photostimulation of the brain of non-human primates. We used a micro-light-emitting diode (LED) array with a flexible polyimide film. The array was combined with a whole-cortex electrocorticographic (ECoG) electrode array for simultaneous photostimulation and recording. Channelrhodopsin-2 (ChR2) was virally transduced into the cerebral cortex of common marmosets, and then the device was epidurally implanted into their brains. We recorded the neural activity during photostimulation of the awake monkeys for 4 months. The neural responses gradually increased after the virus injection for ~8 weeks and remained constant for another 8 weeks. The micro-LED and ECoG arrays allowed semi-invasive simultaneous stimulation and recording during long-term implantation in the brains of non-human primates. The development of this device represents substantial progress in the field of optogenetic applications.

Four-Wire Interface ASIC for a Multi-Implant Link.

This paper describes an on-chip interface for recovering power and providing full-duplex communication over an AC-coupled 4-wire lead between active implantable devices. The target application requires two modules to be implanted in the brain (cortex) and upper chest; connected via a subcutaneous lead. The brain implant consists of multiple identical “optrodes” that facilitate a bidirectional neural interface (electrical recording and optical stimulation), and the chest implant contains the power source (battery) and processor module. The proposed interface is integrated within each optrode ASIC allowing full-duplex and fully-differential communication based on Manchester encoding. The system features a head-to-chest uplink data rate (up to 1.6 Mbps) that is higher than that of the chest-to-head downlink (100 kbps), which is superimposed on a power carrier. On-chip power management provides an unregulated 5-V dc supply with up to 2.5-mA output current for stimulation, and two regulated voltages (3.3 and 3 V) with 60-dB power supply rejection ratio for recording and logic circuits. The 4-wire ASIC has been implemented in a 0.35-n}{}mu text{m} CMOS technology, occup-ying a 1.5-mm2 silicon area, and consumes a quiescent current of n}{}91.2~mu text{A} . The system allows power transmission with measured efficiency of up to 66% from the chest to the brain implant. The downlink and uplink communication are successfully tested in a system with two optrodes and through a 4-wire implantable lead.

Recording nerve signals in canine sciatic nerves with a flexible penetrating microelectrode array

Objective. Previously, we presented the fabrication and characterization of a flexible penetrating microelectrode array (FPMA) as a neural interface device. In the present study, we aim to prove the feasibility of the developed FPMA as a chronic intrafascicular recording tool for peripheral applications. Approach. For recording from the peripheral nerves of medium-sized animals, the FPMA was integrated with an interconnection cable and other parts that were designed to fit canine sciatic nerves. The uniformity of tip exposure and in vitro electrochemical properties of the electrodes were characterized. The capability of the device to acquire in vivo electrophysiological signals was evaluated by implanting the FPMA assembly in canine sciatic nerves acutely as well as chronically for 4 weeks. We also examined the histology of implanted tissues to evaluate the damage caused by the device. Main results. Throughout recording sessions, we observed successful multi-channel recordings (up to 73% of viable electrode channels) of evoked afferent and spontaneous nerve unit spikes with high signal quality (SNR > 4.9). Also, minor influences of the device implantation on the morphology of nerve tissues were found. Significance. The presented results demonstrate the viability of the developed FPMA device in the peripheral nerves of medium-sized animals, thereby bringing us a step closer to human applications. Furthermore, the obtained data provide a driving force toward a further study for device improvements to be used as a bidirectional neural interface in humans.

Flexible Optoelectric Neural Interface Integrated Wire-Bonding $\mu$ LEDs and Microelectrocorticography for Optogenetics

As an advanced brain–computer interface, the flexible surface electrode array has been used for spatiotemporal localization of neural interactions by recording electrocorticography (ECoG) signals over brain cortical areas. Compared with the electrical stimulation, optogenetics provides a potentially ideal way to stimulate the genetically modified brain tissue by light. In this paper, we developed an optoelectric neural interface combining a micro ECoG ( $\mu $ ECoG) recording electrode array and a microlight-emitting diode ( $\mu $ LED) array. Three $\mu $ LED chips were connected to a flexible polyimide substrate by a unique wire bonding method, and their light-emitting surfaces were downward and in the same plane with the substrate’s lower surface, which allowed blue light directly going through the aligned holes on substrate with barely no loss. In addition, the recording electrodes were modified with electroplated platinum black or activated iridium oxide, and their stability was proved well after repetitive pressures. Mechanical strength and conformality of two $\mu $ ECoG arrays with 5 and $10~\mu \text{m}$ thicknesses were tested. Finally, this bidirectional neural interface was proved to be effective by an acute in vivo experiment performed by attaching two devices with varied thicknesses to the cortical surface of a mouse expressing Channelrhodopsin-2.

Compact silicon-based optrode with integrated laser diode chips, SU-8 waveguides and platinum electrodes for optogenetic applications

We report on a compact optrode, i.e. a MEMS-based, invasive, bidirectional neural interface allowing to control neural activity using light while neural signals are recorded nearby. The optrode consists of a silicon (Si) base carrying two pairs of bare laser diodes (LDs) emitting at 650 nm and of two 8 mm-long, 250 µm-wide and down to 50 µm-thick shanks extending from the base. Each LD is efficiently coupled to one of four 15 or 20 µm-wide and 13 µm-high SU-8 waveguides (WGs) running in pairs along the shanks. In addition, each shank comprises four 20 µm-diameter platinum electrodes for neural recording near the WG end facets. After encapsulation of the LDs with a Si cover chip blocking stray light and protecting the LDs from the harsh environment to which the probe is destined, the compact base measures only 4 × 4 × 0.43 mm3. The time averaged radiant emittance at the WG end facet is 96.9 mW mm−2 for an LD current of 35 mA at a duty cycle of 5%. The absolute electrode impedance at 1 kHz is 1.54 ± 0.06 MΩ. Using infrared thermography, the temperature increase of the probe during LD operation was determined to be about 1 K under neuroscientifically relevant operating conditions.

A 128-Channel FPGA-Based Real-Time Spike-Sorting Bidirectional Closed-Loop Neural Interface System.

A multichannel neural interface system is an important tool for various types of neuroscientific studies. For the electrical interface with a biological system, high-precision high-speed data recording and various types of stimulation capability are required. In addition, real-time signal processing is an important feature in the implementation of a real-time closed-loop system without unwanted substantial delay for feedback stimulation. Online spike sorting, the process of assigning neural spikes to an identified group of neurons or clusters, is a necessary step to make a closed-loop path in real time, but massive memory-space requirements commonly limit hardware implementations. Here, we present a 128-channel field-programmable gate array (FPGA)-based real-time closed-loop bidirectional neural interface system. The system supports 128 channels for simultaneous signal recording and eight selectable channels for stimulation. A modular 64-channel analog front-end (AFE) provides scalability and a parameterized specification of the AFE supports the recording of various electrophysiological signal types with 1.59 ± 0.76 root-mean-square noise. The stimulator supports both voltage-controlled and current-controlled arbitrarily shaped waveforms with the programmable amplitude and duration of pulse. An empirical algorithm for online real-time spike sorting is implemented in an FPGA. The spike-sorting is performed by template matching, and templates are created by an online real-time unsupervised learning process. A memory saving technique, called dynamic cache organizing, is proposed to reduce the memory requirement down to 6 kbit per channel and modular implementation improves the scalability for further extensions.

Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.

OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation paradigms. Clinical trial registration no.: NCT01934296 (clinicaltrials.gov).

A bidirectional neural interface CMOS analog front-end IC with embedded isolation switch for implantable devices

A bidirectional neural interface analog front-end IC with both stimulation and recording functions is implemented using 0.18-µm standard CMOS process. The proposed IC is comprised of a bipolar biphasic neural stimulator using a transistor-stacked current-mirror driver to achieve good current matching performance in stimulation mode and low-voltage capacitive feedback neural amplifiers for recording mode. In order to save die area, high-voltage isolation switches are embedded within the stimulator core to protect the low-voltage recording circuits from damage. Despite using a low-voltage process, the stimulator is able to deliver up to 1mA current through 10kΩ load using 12.8V supply voltage and the recording amplifier uses 0.8V supply voltage while consuming 1µA of current. The complete IC occupies 0.29mm2 of die area and can be applied for various multi electrode array interface bidirectional neural SoCs in medical implant devices.

A Bidirectional Neural Interface IC With Chopper Stabilized BioADC Array and Charge Balanced Stimulator.

We present a bidirectional neural interface with a 4-channel biopotential analog-to-digital converter (bioADC) and a 4-channel current-mode stimulator in 180 nm CMOS. The bioADC directly transduces microvolt biopotentials into a digital representation without a voltage-amplification stage. Each bioADC channel comprises a continuous-time first-order ∆Σ modulator with a chopper-stabilized OTA input and current feedback, followed by a second-order comb-filter decimator with programmable oversampling ratio. Each stimulator channel contains two independent digital-to-analog converters for anodic and cathodic current generation. A shared calibration circuit matches the amplitude of the anodic and cathodic currents for charge balancing. Powered from a 1.5 V supply, the analog and digital circuits in each recording channel draw on average [Formula: see text] and [Formula: see text] of supply current, respectively. The bioADCs achieve an SNR of [Formula: see text] and a SFDR of [Formula: see text] , for better than 9-b ENOB. Intracranial EEG recordings from an anesthetized rat are shown and compared to simultaneous recordings from a commercial reference system to validate performance in-vivo . Additionally, we demonstrate bidirectional operation by recording cardiac modulation induced through vagus nerve stimulation, and closed-loop control of cardiac rhythm. The micropower operation, direct digital readout, and integration of electrical stimulation circuits make this interface ideally suited for closed-loop neuromodulation applications.

Investigation on the hermeticity of an implantable package with 32 feedthroughs for neural prosthetic applications.

This paper presents an implantable package aimed at hosting a bidirectional neural interface for neural prosthetic applications. The package has been conceived to minimize the invasivity for the patient, for this reason a cylindrical container with an outer diameter of 7 mm and a length of 21 mm has been designed. The package, realized in alumina (Al2O3), presents 32 hermetic feedthroughs located at the top and bottom base of the cylinder. The hermetic housing has been assembled using a low-temperature soldering method based on a previous platinum/gold (Pt/Au) metallization of the ceramic parts. The package's hermeticity has been successfully proved by means of in-vitro tests, exhibiting an increase in the inner relative humidity of 20 %RH over 75 days of observation.

Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease.

Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for the generation of dyskinesia as well as a promising control signal for closed-loop DBS. Oscillations in brain networks link functionally related brain areas to accomplish thought and action, but this mechanism may be altered or exaggerated by disease states. Invasive recording using implanted electrodes provides a degree of spatial and temporal resolution that is ideal for analysis of network oscillations. Here we used a novel, totally implanted, bidirectional neural interface for chronic multisite brain recordings in humans with Parkinson's disease. We characterized an oscillation between cortex and subcortical modulators that is associated with a serious adverse effect of therapy for Parkinson's disease: dyskinesia. The work shows how a perturbation in oscillatory dynamics might lead to a state of excessive movement and also suggests a possible biomarker for feedback-controlled neurostimulation to treat hyperkinetic disorders.

A Bidirectional Neural Interface Circuit With Active Stimulation Artifact Cancellation and Cross-Channel Common-Mode Noise Suppression

This work presents a bidirectional neural interface circuit that enables simultaneous recording and stimulation with a stimulation artifact cancellation circuit. The system employs a common average referencing (CAR) front-end circuit to suppress cross-channel environmental noise to further facilitate use in clinical environment. This paper also introduces a new range-adapting (RA) SAR ADC to lower the system power consumption. A prototype is fabricated in $0.18\;\mu {\rm{m}}$ CMOS and characterized and tested in vivo in an epileptic rat model. The prototype attenuates stimulation artifacts by up to 42 dB and suppresses cross-channel noise by up to 39.8 dB. The measured power consumption per channel is 330 nW, while the area per channel is 0.17 mm $^2$ .